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Triostin a derived cyclopeptide as architectural template for the alignment of four recognition units.

ABSTRACT: The DNA bisintercalator triostin A is structurally based on a disulfide-bridged depsipeptide scaffold that provides preorganization of two quinoxaline units in 10.5 Å distance. Triostin A analogues are synthesized with nucleobase recognition units replacing the quinoxalines and containing two additional recognition units in between. Thus, four nucleobase recognition units are organized on a rigid template, well suited for DNA double strand interactions. The new tetra-nucleobase binders are synthesized as aza-TANDEM derivatives lacking the N-methylation of triostin A and based on a cyclopeptide backbone. Synthesis of two tetra-nucleobase aza-TANDEM derivatives is established, DNA interaction analyzed by microscale thermophoresis, cytotoxic activity studied and a nucleobase sequence dependent self-aggregation investigated by mass spectrometry.

SUBMITTER: Kotyrba UM

PROVIDER: S-EPMC4232271 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Triostin a derived cyclopeptide as architectural template for the alignment of four recognition units.

Kotyrba Ursula M UM Pröpper Kevin K Sachs Eike-F EF Myanovska Anastasiya A Joppe Tobias T Lissy Friederike F Sheldrick George M GM Koszinowski Konrad K Diederichsen Ulf U

ChemistryOpen 20140709 4

The DNA bisintercalator triostin A is structurally based on a disulfide-bridged depsipeptide scaffold that provides preorganization of two quinoxaline units in 10.5 Å distance. Triostin A analogues are synthesized with nucleobase recognition units replacing the quinoxalines and containing two additional recognition units in between. Thus, four nucleobase recognition units are organized on a rigid template, well suited for DNA double strand interactions. The new tetra-nucleobase binders are synth ...[more]

PMID: 25478311

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